Abstract
BackgroundThe molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1).MethodsWe developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504). Samples from systemic sclerosis patients (n = 99) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n = 656).ResultsPlasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score.ConclusionsOur sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte–macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in clinical trials.
Highlights
The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options
Soluble SIGLEC-1 assay development To investigate whether we could detect SIGLEC-1 expression levels in peripheral blood, we developed an immunoassay based on time-resolved fluorescence (TRF) to measure the concentrations of the circulating form of the receptor, which we refer to as sSIGLEC-1
We found that sSIGLEC-1 was detected in the circulation, with concentrations ranging from 1.29 to 276.1 ng/ml in plasma/serum samples from healthy donors and systemic lupus erythematosus (SLE) patients
Summary
The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. The type I interferon (IFN) pathway was identified as a central feature of the autoimmune disease systemic lupus erythematosus (SLE) when IFN-α was first detected at high levels in patients’ sera [1]. Since this initial observation, the development of SLE-like clinical manifestations in patients treated with IFN-α for different malignancies pointed to the involvement of IFN-α in the aetiology of the disease [2]. This is relevant to IFN-driven diseases, as IFN-α is known to significantly alter the relative distribution of immune cell types in blood, which can severely compromise the diagnostic potential of the whole blood IFN signature [8] and lead to the observed lack of correlation between the signature and disease activity over time [9, 10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
